Chlamydophila pneumoniae (C. pneumoniae), formerly known as Chlamydia pneumoniae (Everett et al. 1999), was first isolated in 1965 and identified 15 years later. (Grayston 2000) and is established as an etiologic agent of respiratory tract diseases and related sequelae (Chirgwin et al. 1991, Grayston et al. 1989, Grayston et al. 1990, Grayston et al. 1994, Gnarpe 1999). C. pneumoniae has been linked to asthma (Hahn 2000), Guillain-Barré syndrome (Haidl et al. 1992), endocarditis, atherosclerotic vascular disease (Ramirez et al. 1996), Kawasaki disease (Normann et al. 1999), chronic obstructive pulmonary disease (Verkooyen 1997, Miyashita et al. 1998), sarcoidosis (Laurila 1997), reactive arthritis (Hannu et al. 1999), and multiple sclerosis (Sriram et al. 1999). Chlamydophila are Gram-negative obligate intracellular bacteria having a biphasic life cycle, consisting of a metabolically inert infectious elementary body (EB) and a metabolically active reticulate body (RB).
C. pneumoniae is a respiratory pathogen believed to cause 5–20% of community-acquired pneumonias and 5% of bronchitis and sinusitis in adults and children (Jolcinen 2001, Wubbel 1999, Ouchi 1999, Porath 1997, Schito 1994). Recent studies suggest that not only does this organism rank as the 3rd most common cause of pneumonia, but also may play a more significant role in the pathogenesis of several chronic diseases including asthma and atherosclerosis. Seroepidemiology has shown that most C. pneumoniae infections are asymptomatic (Aldous, Wang, Foy, Grayston 1990). Regional and international serology-based epidemiologic studies of C. pneumoniae have shown a high prevalence and ubiquitous infection. These studies have indicated that most people have had their first C. pneumoniae infection before age 20, and reinfection is common.
The biphasic life cycle and intracellular host cell parasitism of chlamydia could allow for maintenance of a chronic infection. It is well established that C. psittici can persist in mammals and birds lifelong, and only occasionally cause disease, most often after some form of stress induction. C. pneumoniae has been demonstrated to multiply in macrophages, endothelia, smooth muscle cells, etc. in vitro. C. pneumoniae multiplication has been associated with cytokine production and induction of adhesions (Kaukoranta et al. 1996, Dechend et al. 1999).
Many laboratory methods have been developed for the diagnosis of C. pneumoniae infection, including primary isolation of the organism in cell culture, serological assays, immunohistochemical assays and polymerase chain reaction (PCR) (Grayston 1992). Despite great effort to improve primary culture techniques of C. pneumoniae, isolation and culture still require specialized personnel and substantial laboratory resources. To date, only a few laboratories worldwide have made human isolates.
Serologic and PCR assays are the tools most often applied for routine diagnosis of acute C. pneumoniae infection. Serologic assays include complement fixation (CF), microimmunofluorescence (MIF), enzyme-linked immunosorbant assay (ELISA), and immunobistochemistry (Bames 1989). These assays require significant technical expertise and are subject to investigator interpretation. The MIF test remains the most sensitive assay, the only species-specific assay, and is considered the current “Gold Standard” for determining prevalence of C. pneumoniae in populations studied (Verkooyen et al. 1998). The traditional MIF assay relies on the use of whole elementary bodies (EB) as an antigen. Though lacking the necessary species specificity for use as a diagnostic serologic test, indirect immunofluorescence assay (IFA) has been used for culture confirmation of isolates or for laboratory culture standardization. IFA relies on both whole RBs and EBs fixed with methanol as antigen in C. pneumoniae infected cell culture. The use of whole C. pneumoniae antigen has been observed by investigators to have cross reactivity in certain serologic and immunohistochemical tests (Brade et al. 1990). Thus, there clearly is a need for assays that identify C. pneumoniae. In addition, there is a need for novel treatments for C. pneumoniae infections such as pneumonia, and vaccines that can prevent such infections.